The aim of this study was to compare the self-reported health-related quality of life (HRQL) of children and adolescents with diabetes, asthma or cystic fibrosis (CF) with the HRQL of a large community sample, to assess the extent to which the HRQL of the children and adolescents with chronic illness changes over time, and to examine the consistency of changes in different HRQL domains. One hundred and twenty three young people aged 10-16 years with asthma, diabetes, or CF were recruited from specialist paediatric clinics. Children rated their HRQL using the Child Health Questionnaire (CHQ) and three disease-specific measures at baseline, 6, 12, 18 and 24 months post-baseline. In several areas, the HRQL of children with chronic illness was significantly worse than that of children in the community sample. Over the 2 years of the study, although children with asthma and diabetes did not report significant changes in CHQ scores rating their physical health, they reported significant improvements in scores rating the extent to which health problems interfered with physical and family activities. CHQ scores describing their physical health reported by children with CF declined significantly but there was no significant change in scores rating interference with physical and family activities.